PEPTIDE AND PROBE MODULATION OF AQUEOUS DYNAMICS

这项建议的目标是1)与 用组织化学和免疫组织化学方法进行体外定位 眼球前段和眼内的各种神经肽 不同选择性分子探针对离子细胞的体外作用 睫状体上皮中的事件与体内生理和 这些药物对眼压的药理作用。 调查将提供有关神经肽(LOW)作用的信息 分子量、生物活性内源蛋白)和分子探针 (细胞离子运输、交换或通道的化学抑制剂) 作为房水的生理调节剂或药物调节剂 动力学。结果将提供对控制因素的洞察 眼压和房水生理正常。新奇而独特 房水动力学的药物操作可能是可能的 具有展示青光眼新疗法的潜力。 药物引起眼内病变的机制 将对压力进行调查。外流的非侵入性测量 设施，巩膜外静脉压和房水流量将 已执行。房水流量、总流出量的侵入性测定 将测量设备、眼部血流量和血流量。 生化测定包括房水蛋白的测定， 抗坏血酸和环磷腺苷浓度。房水动力学研究 在局部、全身、房内或玻璃体内实施 行政管理。 待研究的神经肽包括加压素和 神经肽Y。注意确定其特异性和 这些药物与经典神经递质的相互作用。在……里面 此外，神经肽AS的体外作用研究 对眼前段肌肉进行调节剂/调节剂 提供关于这些自然产生的多肽的更多信息 荷尔蒙。分子探针阿米洛利(钠转运抑制剂) 和阿帕明(钾转运抑制剂)将被研究其 对眼压的影响。

The objectives of this proposal are the correlation of 1) the in vitro localization by histochemical and immunohistochemical methods of various neuropeptides in the anterior segment of the eye and 2) the in vitro effects of various selective molecular probes on ionic cellular events in the ciliary epithelium with the in vivo physiological and pharmacological effects of these agents on intraocular pressure. Investigations will provide information on the role of neuropeptides (low molecular weight, bioactive endogenous proteins) and molecular probes (chemical inhibitors of cellular ionic transport, exchange, or channels) as physiologic regulators or pharmacologic modulators of aqueous humor dynamics. Results will provide insights into factors controlling intraocular pressure and normal aqueous humor physiology. New and unique pharmacologic manipulations of aqueous humor dynamics may be possible with the potential for the demonstration of new therapies for glaucoma. Mechanisms responsible for drug-induced alterations in intraocular pressure will be investigated. Noninvasive measurements of outflow facility, episcleral venous pressure and aqueous humor flow will be performed. Invasive determination of aqueous humor flow, total outflow facility, and ocular blood flow and volume, will be measured. Biochemical determinations include measurement of aqueous humor protein, ascorbate, and cyclic AMP concentration. Aqueous humor dynamic studies are performed following topical, systemic, intracameral, or intravitreal administration. Neuropeptides to be investigated include vasopressin and neuropeptide Y. Attention is directed to determining the specificity and the interaction of these agents with classical neurotransmitters. In addition, in vitro studies of the effects of neuropeptides as regulators/modifiers on anterior segment smooth muscles will be performed to provide additional information on these naturally occurring peptide hormones. The molecular probes amiloride (sodium transport inhibitor) and apamin (potassium transport inhibitor) will be investigated for their effect on intraocular pressure.